Two-component system HprS/HprR enhances kidney colonization of uropathogenic Escherichia coli CFT073 by increasing flagellar expression.

Urinary tract infections (UTIs) are predominantly caused by uropathogenic Escherichia coli (UPEC) and occur via an ascending route. UPEC invades bladder epithelial cells, causing cystitis and ascends to the kidneys, inducing pyelonephritis. Flagella-mediated motility is critical for this dissemination. The fliLMNOPQR operon encodes essential flagellar components, which are required for flagellar motility. However, the regulatory mechanisms that activate the expression of flagellar genes, facilitating bacterial motility in response to host cues, remain unclear. This study reported that the two-component system HprSR directly activates fliLMNOPQR expression, promoting UPEC kidney colonization in response to host-derived reactive oxygen species (ROS) and reactive chlorine species (RCS). The hprSR mutation impairs UPEC kidney colonization due to reduced expression of flagellar genes. Neutralization of ROS and RCS in the mouse urinary tract prevents kidney colonization by inactivating HprSR. This study reveals a regulatory pathway in which host-derived signals activate UPEC virulence to mediate kidney colonization.